The BTK inhibitor zanubrutinib has demonstrated “robust activity” and “good tolerability” in patients with Waldenström macroglobulinemia (WM), according to an investigator.
In a phase 1 trial, zanubrutinib produced an overall response rate (ORR) of 92%, and the estimated 12-month progression-free survival (PFS) rate was 89%.
Most adverse events (AEs) in this trial were grade 1 or 2 in severity, although the incidence of serious AEs was 42%.
, of the Peter MacCallum Cancer Center in Victoria, Australia, presented these results at the 10th International Workshop on Waldenström’s Macroglobulinemia.
The trial is sponsored by BeiGene, the company developing zanubrutinib.
The trial () includes patients with WM and other B-cell malignancies. As of July 24, 2018, 77 patients with treatment-naive or relapsed/refractory WM had been enrolled. Of those patients, 73 were evaluable for efficacy in this analysis, and the median follow-up time was 22.5 months.
At the time of the data cutoff, 62 patients remained on study treatment. Four patients (3%) discontinued treatment because of disease progression, and one patient remains on treatment after progression.
The median time to response was 85 days. The ORR was 92%, and the major response rate (MRR) was 82%. Of patients in the analysis, 41% achieved a very good partial response (VGPR), defined as a greater than 90% reduction in baseline immunoglobulin M (IgM) levels and improvement of extramedullary disease by computed tomography.
The median IgM decreased from 32.7 g/L at baseline to 8.2 g/L. The median hemoglobin increased from 8.85 g/dL to 13.4 g/dL among 32 patients with hemoglobin less than 10 g/dL at baseline.
MYD88 genotype was known in 63 patients. In the subset known to have the MYD88L265P mutation (n = 54), the ORR was 94%, the MRR was 89%, and the VGPR rate was 46%. In the nine patients known to have wild-type MYD88 (a genotype that, historically, has had suboptimal response to BTK inhibition), the ORR was 89%, the MRR was 67%, and the VGPR rate was 22%.
The 12-month PFS was estimated to be 89%, and the median PFS had not been reached.
The most frequent AEs of any attribution were petechiae/purpura/contusion (43%), upper respiratory tract infection (42%), cough (17%), diarrhea (17%), constipation (16%), back pain (16%), and headache (16%). Grade 3-4 AEs of any attribution reported in three or more patients included neutropenia (9%), anemia (7%), hypertension (5%), basal cell carcinoma (5%), renal and urinary disorders (4%), and pneumonia (4%). Serious AEs were seen in 32 patients (42%). Events in five patients (7%) were considered possibly related to zanubrutinib treatment – febrile neutropenia, colitis, atrial fibrillation, hemothorax, and pneumonia. Atrial fibrillation/flutter occurred in four patients (5%), and major hemorrhage was observed in two patients (3%).
“We are encouraged that additional data on zanubrutinib in patients with WM confirms the initially reported experience with consistent demonstration of robust activity and good tolerability,” Dr. Tam said in a.
The trial is sponsored by BeiGene. Dr. Tam reported financial relationships with BeiGene and other companies.